Stimulation of bradykinin B(1) receptors induces vasodilation in conductance and resistance coronary vessels in conscious dogs: comparison with B(2) receptor stimulation.

BACKGROUND: Constitutive bradykinin B(1) receptors have been identified in dogs; however, their physiological implications involving the coronary circulation remain to be determined. This study examined, in conscious dogs, the coronary response to des-Arg(9)-bradykinin (a B(1) receptor agonist) and the mechanisms involved. METHODS AND RESULTS: Eleven dogs were instrumented with a left ventricular micromanometer, a circumflex coronary catheter, a cuff occluder, a Doppler flow probe, and ultrasonic crystals to measure coronary blood flow velocity (CBFv) and coronary diameter (CD). Intracoronary des-Arg(9)-bradykinin (3 to 100 ng/kg) and bradykinin (0.1 to 10 ng/kg) did not modify systemic hemodynamics but dose-dependently increased CBFv and CD. Des-Arg(9)-bradykinin was less potent than bradykinin. Hoe 140 (a B(2) antagonist, 10 microg/kg) abolished the effects of bradykinin but did not influence the effects of des-Arg(9)-bradykinin. When CBFv increase was prevented by the cuff occluder, CD responses to bradykinin and des-Arg(9)-bradykinin were maintained. Intracoronary lisinopril (0. 75 mg) increased the CD response to bradykinin, with only minimal effect on CBFv, and extended the duration of the effect. Lisinopril did not alter des-Arg(9)-bradykinin responses. Intracoronary N(omega)-nitro-L-arginine (2 mg/kg) decreased the CD effect of bradykinin and prevented the CBFv and CD effects of des-Arg(9)-bradykinin. The relaxing effect of des-Arg(9)-bradykinin on isolated coronary rings was prevented by des-Arg(9), [Leu(8)]-bradykinin. CONCLUSIONS: In the conscious dog, B(1) receptors are present in coronary vessels, and their stimulation produces vasodilation in conductance and resistance vessels, which is mediated essentially by NO but not modulated by angiotensin-converting enzyme. However, the coronary vasodilation induced by B(1) receptor stimulation is not as great as that produced by B(2) receptor stimulation.

Alteration of left ventricular diastolic function during coronary angioplasty-induced ischemia: a color M-mode Doppler study.

OBJECTIVES: The aim of this study was to assess the effects of ischemia on diastolic function by analyzing flow propagation velocity with color M-mode Doppler echocardigraphy. BACKGROUND: Color M-mode Doppler echocardiography has been proposed as a method of assessing left ventricular filling. METHODS: Color M-mode Doppler echocardiography and measurement of hemodynamic data were performed simultaneously at baseline and during angioplasty-induced ischemia. Tau was compared with flow propagation velocity. Late diastolic indexes, left ventricular pressure and flow cessation time were also investigated. RESULTS: During ischemia, left ventricular relaxation rate (tau) increased, whereas flow propagation velocity decreased, from (mean +/- SD) 46.8 +/- 10 ms to 72.6 +/- 18.3 ms and from 59.8 +/- 15.8 cm/s to 30 +/- 8 cm/s, respectively (all p < 0.0001). The maximal slowing of flow propagation velocity was observed 20 to 30 s after the beginning of the inflation, coexisting with a notch on the ascending limb of the negative rate of rise of the left ventricular pressure (dP/dt) curve. Flow propagation velocity was correlated with tau both at baseline (r = 0.53, p < 0.05) and during inflation (r = 0.53, p < 0.03). Left ventricular end-diastolic pressure increased during ischemia from 13.5 +/- 8 mm Hg at baseline to 27.5 +/- 7 mm Hg, while a premature cessation of the entering flow occurred -13.8 +/- 23 ms before the next Q wave onset, compared with 4.5 +/- 19.6 ms after the Q wave onset at baseline (all p < 0.0001). CONCLUSIONS: The analysis of flow propagation velocity showed that early filling is highly dependent on left ventricular relaxation rate, particularly through the phenomenon of asynchrony. During ischemia, the premature cessation of late filling is associated with increased diastolic pressures.

Effects of bradykinin on coronary blood flow and vasomotion in transplant patients.

OBJECTIVES: To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine. BACKGROUND: Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs. METHODS: Sixteen HTXs were compared 3.6 +/- 1.7 months after transplantation to seven control subjects. Coronary flow velocity was measured using guide-wire Doppler. Diameters (D) of three segments of the left coronary artery and coronary blood flow (CBF) were assessed at baseline, after 3-min infusions of increasing bradykinin doses (50, 150 and 250 ng/min) then of increasing acetylcholine doses (estimated blood concentrations of 10(-8), 10(-7) and 10(-6) M). RESULTS: Bradykinin induced similar dose-dependent increases in D and CBF in both groups: D was 11 +/- 12%, 19 +/- 14% and 22 +/- 16% (all p < 0.0001), and CBF was 50 +/- 40%, 130 +/- 68% and 186 +/- 77% (all p < 0.0001). Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in HTX, as well as a marked increase in CBF in both groups. Acute allograft rejection, present in 8 of the 16 HTXs, did not modify responses to bradykinin, but was associated with a smaller CBF increase in response to acetylcholine (p < 0.05). CONCLUSIONS: The coronary vasodilating effects of bradykinin are preserved early after heart transplantation, even in the presence of acute allograft rejection. Although there is an abnormal vasoconstricting response to acetylcholine reflecting endothelium dysfunction, the endothelium remains a functionally active organ in heart transplant recipients.

Endogenous sodium-potassium-chloride cotransport inhibitor in congestive heart failure.

OBJECTIVES: This study sought to evaluate the relation, if any, between fluid overload in congestive heart failure (CHF) and a newly discovered endogenous natriuretic factor acting like loop diuretic drugs: cotransport inhibitory factor (CIF). BACKGROUND: The humoral mechanisms regulating volume overload in CHF are not fully understood. Therefore, we investigated whether there is a role for CIF in this pathologic condition. METHODS: Plasma and urinary CIF levels were investigated in 23 patients with chronic CHF and compared with changes in plasma atrial natriuretic peptide (ANP). Twelve patients without CHF served as control subjects. RESULTS: CHF was associated with a highly significant threefold increase in both plasma CIF levels (mean +/- SD 7.10 +/- 3.01 vs. 2.28 +/- 0.92 U/ml, p < 0.0001) and urinary CIF excretion (7,849 +/- 3,600 vs. 2,351 +/- 1,297 U/day, p < 0.0001) with respect to patients without CHF. CIF increased as a function of impairment in left ventricular ejection fraction (r = -0.703, p < 0.0001) and the severity of clinical status. Plasma ANP was also increased in patients with CHF, although to a lesser extent (68%, p = 0.0501) than plasma CIF, and was also significantly correlated with left ventricular ejection fraction (r = -0.552, p = 0.0004). CONCLUSIONS: Plasma and urinary CIF activities were strongly and very significantly increased in chronic CHF. In addition to ANP, this long-term natriuretic agent may be of potential importance in reducing fluid overload in CHF.

Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty. The PREDICT Trial Investigators. Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty.

OBJECTIVES: This study sought to determine whether pravastatin affects clinical or angiographic restenosis after coronary balloon angioplasty. BACKGROUND: Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. METHODS: In a multicenter, randomized, double-blind trial, 695 patients were randomized to receive pravastatin (40 mg/day) or placebo for 6 months after successful balloon angioplasty. All patients received aspirin (100 mg/day). The primary angiographic end point was minimal lumen diameter (MLD) at follow-up, assessed by quantitative coronary angiography. A sample size of 313 patients per group was required to demonstrate a difference of 0.13 mm in MLD between groups (allowing for a two-tailed alpha error of 0.05 and a beta error of 0.20). To allow for incomplete angiographic follow-up (estimated lost to follow-up rate of 10%), 690 randomized patients were required. Secondary end points were angiographic restenosis rate (restenosis assessed as a categoric variable, > 50% stenosis) and clinical events (death, myocardial infarction, target vessel revascularization). RESULTS: At baseline, clinical, demographic, angiographic and lipid variables did not differ significantly between groups. In patients treated with pravastatin, there was a significant reduction in total and low density lipoprotein cholesterol and triglyceride levels and a significant increase in high density lipoprotein cholesterol levels. At follow-up the MLD (mean +/- SD) was 1.47 +/- 0.62 mm in the placebo group and 1.54 +/- 0.66 mm in the pravastatin group (p = 0.21). Similarly, late loss and net gain did not differ significantly between groups. The restenosis rate (recurrence > 50% stenosis) was 43.8% in the placebo group and 39.2% in the pravastatin group (p = 0.26). Clinical restenosis did not differ significantly between groups. CONCLUSIONS: Although pravastatin has documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, this study shows that it has no effect on angiographic outcome at the target site 6 months after coronary angioplasty.

Prediction of functional recovery of viable myocardium after delayed revascularization in postinfarction patients: accuracy of dobutamine stress echocardiography and influence of long-term vessel patency.

OBJECTIVES: We sought to evaluate dobutamine stress echocardiography (DSE) for predicting recovery of viable myocardium after revascularization with cineangiography as a gold standard for left ventricular (LV) function. We studied the influence of late vessel reocclusion on regional LV function. BACKGROUND: Dobutamine stress echocardiography is a well established evaluation method for myocardial viability assessment. In previous studies the reference method for assessing LV recovery was echocardiography, long-term vessel patency has not been systematically addressed. METHODS: Sixty-eight patients with a first acute myocardial infarction (AMI) and residual stenosis of the infarct related artery (IRA) underwent DSE (mean +/- standard deviation) 21 +/- 12 days after AMI to evaluate myocardial viability. Revascularization of the IRA was performed in 54 patients by angioplasty (n = 43) or bypass grafting (n = 11). Coronary angiography and LV cineangiography were repeated at four months to assess LV function and IRA patency. RESULTS: Sensitivity and specificity of DSE for predicting myocardial recovery after revascularization were 83% and 82%. In the case of late IRA patency, specificity increased to 95%, whereas sensitivity remained unchanged. In the 16 patients with myocardial viability and late IRA patency, echocardiographic wall motion score index decreased after revascularization from 1.83 +/- 0.15 to 1.36 +/- 0.17 (p = 0.0001), and left ventricular ejection fraction (LVEF) increased from 0.52 +/- 0.06 to 0.57 +/- 0.06 (p = 0.0004), whereas in five patients, reocclusion of the IRA prevented improvement of segmental or global LV function despite initially viable myocardium. CONCLUSIONS: Dobutamine stress echocardiography is reliable to predict recovery of viable myocardium after revascularization in postinfarction patients. Late reocclusion of the IRA may prevent LV recovery and influence the accuracy of DSE.

Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients.

OBJECTIVE: To determine the long-term efficacy and safety of a fixed, very-low-dose tablet combining one-half the standard dose of perindopril with one-quarter the standard dose of indapamide as first-line treatment in elderly patients. DESIGN: Double-blind, randomized, placebo-controlled study in an outpatient setting. PATIENTS AND INTERVENTIONS: Following a single-blind, placebo run-in period of 4 weeks, patients [65-85 years, with mild-to-moderate essential hypertension or isolated systolic hypertension (ISH)] were randomized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg (Per/ Ind) (n=193) or placebo (n=190), daily for 12 weeks. After this first 12-week period, all patients on Per/Ind (n=138) and patients responding to placebo (n=61) were maintained on their previous regimen for a further 48 weeks. Patients in the placebo group whose blood pressure was not normalized, were switched to Per/Ind (n=60). MAIN OUTCOME MEASURE: The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60. RESULTS: After 1 year of treatment (intention-to-treat) supine systolic and diastolic blood pressure decreased by 23.0 +/- 15.3 mmHg and 13.3 +/- 94 mmHg with Per/Ind (n=253: 193 from randomized Per/Ind group and 60 from the placebo group switched at week 12). The mean decreases in systolic blood pressure were similar in essential hypertension and ISH (systolic blood pressure 23.2 versus 22.7 mmHg, respectively). Per/Ind treatment (n=253) achieved an initial normalization of blood pressure in 96.2% [95% confidence interval (CI) 93.6-98.9%; Kaplan-Meier estimate] of Per/Ind-treated patients; 79.8% (95% CI 74.1-85.5%) of these maintained a normalized blood pressure throughout the 1 -year follow-up. The incidence of adverse events was similarly low in the placebo and active therapy groups. Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects CONCLUSIONS: The fixed, very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year, and is well-tolerated.

Study population and treatment titration in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

OBJECTIVES: To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). To determine the success of single and combination therapy in achieving target blood pressures in such a population. DESIGN: INSIGHT is a double-blind, prospective outcome trial comparing the efficacy of the calcium channel blocker, nifedipine GITS, and the thiazide, co-amilozide, in preventing myocardial infarction and stroke. We recruited 2996 men and 3454 women, aged 55-80 years, with blood pressure during placebo run-in >150/95 mmHg or isolated systolic blood pressure >160 mmHg from nine countries. Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide (hydrochlorothiazide 25 mg/amiloride 5 mg) once daily was performed by minimization rather than randomization to balance additional risk factors. This was followed by four optional increases in treatment: dose-doubling of the primary drug, addition of atenolol 25/50 mg or enalapril 5/10 mg, and then any other hypotensive drug excluding calcium blockers or diuretics. Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg. RESULTS: Blood pressure at randomization was 172+/-15 / 99+/-9 mmHg. Thirteen per cent of the patients were previously untreated. The proportions of each additional risk factors were: smoking > 10/day, 29%; cholesterol > 6.43 mmol/l, 52%; family history of premature myocardial infarction or stroke, 21%; diabetes mellitus 20%; left ventricular hypertrophy, 10%; previous myocardial infarction, other presentations of coronary heart disease, and peripheral vascular disease, each 6%; proteinuria, 3%. Fifty-five per cent of patients had one additional risk factor, whereas 33%, 9% and 3% had two, three or more additional risk factors, respectively. The blood pressure (and falls in blood pressure) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg (33+/-15 / 17+/-9) in the 5226 patients still on randomized treatment The numbers requiring the four treatment increments were, respectively, 1591, 780, 597 and 294, meaning that almost 70% of patients on randomized treatment in INSIGHT are receiving only the primary drug. At one year, 69% of patients had a blood pressure < or = 140/90 mmHg. CONCLUSION: INSIGHT is one of the first double-blind comparisons of active antihypertensive treatments, requiring high-risk patients to achieve sufficient power. Despite this requirement, it is possible to achieve good blood pressure control in most patients without the addition of multiple additional treatments that may dilute any differences between the primary agents.

Diagnostic value of image processing in myocardial scintigraphy.

The diagnostic value of stress myocardial analog scintigrams, and of five image-processing methods, was assessed by a decisional analysis in 96 patients undergoing coronary arteriography. The methods involved digitalization, nine-point binomial smoothing, background subtraction by linear interpolation, stationary filtering, and a combination of them. The difference between after-test probabilities of having the disease with a positive or a negative examination provided a discriminant index for different prevalences of the disease. Though the processing methods failed to improve the detection of a circumflex stenosis, the stationary filter significantly increased the diagnostic value for the detection of stenosis in a left anterior descending artery for a large range of prevalence, and in a right coronary artery at high prevalence. Thus, the filter seemed to provide a useful tool for enhancing the diagnostic value of myocardial scintigraphy.

Sympathetic nerve alterations assessed with 123I-MIBG in the failing human heart.

UNLABELLED: Norepinephrine (NE) reuptake function is impaired in heart failure and this may participate in myocyte hyperstimulation by the neurotransmitter. This alteration can be assessed by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. METHODS: To determine whether the impairment of neuronal NE reuptake was reversible after metoprolol therapy, we studied 18 patients (43+/-7 y) with idiopathic dilated cardiomyopathy who were stabilized at least for 3 mo with captopril and diuretics. Patients underwent, before and after 6 mo of therapy with metoprolol, measurements of radionuclide left ventricular ejection fraction (LVEF), maximal oxygen consumption and plasma NE concentration. The cardiac adrenergic innervation function was scintigraphically assessed with MIBG uptake and release measurements on the planar images obtained 20 min and 4 h after tracer injection. To evaluate whether metoprolol had a direct interaction with cardiac MIBG uptake and release, six normal subjects were studied before and after a 1-mo metoprolol intake. RESULTS: In controls, neither cardiac MIBG uptake and release nor circulating NE concentration changed after the 1-mo metoprolol intake. Conversely, after a 6-mo therapy with metoprolol, patients showed increased cardiac MIBG uptake (129%+/-10% versus 138%+/-17%; P = 0.009), unchanged cardiac MIBG release and decreased plasma NE concentration (0.930+/-412 versus 0.721+/-0.370 ng/mL; P = 0.02). In parallel, patients showed improved New York Heart Association class (2.44+/-0.51 versus 2.05+/-0.23; P = 0.004) and increased LVEF (20%+/-8% versus 27%+/-8%; P = 0.0005), whereas maximal oxygen uptake remained unchanged. CONCLUSION: Thus, a parallel improvement of myocardial NE reuptake and of hemodynamics was observed after a 6-mo metoprolol therapy, suggesting that such agents may be beneficial in heart failure by directly protecting the myocardium against excessive NE stimulation.

Assessment of coronary reserve in man: comparison between positron emission tomography with oxygen-15-labeled water and intracoronary Doppler technique.

This study compared positron emission tomography (PET) using oxygen-15-labeled water for measurement of coronary reserve with intracoronary Doppler in patients with left anterior descending artery stenosis and patients with no coronary lesion and a coronary reserve 3 as assessed by the invasive technique. To determine whether PET measurement of coronary reserve is altered by partial volume effect, patients with left ventricular dysfunction due to idiopathic cardiomyopathy were studied with both techniques. Direct ultrasonic measurement of coronary reserve was performed the day prior to the PET study: a Doppler catheter was placed in the proximal left anterior descending artery; mean velocity was recorded at baseline and after dipyridamole administration. Using a time-of-flight PET system, patients underwent: (1) an intravenous bolus of oxygen-15-labeled water at baseline and 4 to 6 min after intravenous infusion of dipyridamole using the same protocol as for Doppler study and (2) a 18F-fluorodeoxyglucose (FDG) myocardial imaging. Oxygen-15 time-activity curves were recorded in myocardial regions of interest (ROIs) drawn on a static FDG image. Using the left ventricular time-activity curve as an input function, a standard model with a single-tissue compartment was fitted to the PET data; myocardial blood flow was estimated as the blood-to-tissue transfer rate constant. Coronary reserve measured by PET was well correlated with the measured by intracoronary Doppler (r = 0.98, p < 0.001 for global population). This PET method is an accurate and reliable tool to noninvasively measure coronary reserve in patients, even in those with left ventricular dysfunction.

MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia.

High altitude hypoxia induces a decrease in the cardiac chronotropic function at maximal exercise or in response to isoproterenol infusion, suggesting an alteration in the cardiac sympathetic activation. Iodine-123 metaiodobenzylguanidine [( 123I]MIBG) was used to map scintigraphically the cardiac sympathetic neuronal function in six male subjects (aged 32 +/- 7 yr) after an exposure to high altitude that created hypoxic conditions. Results obtained just after return to sea level (RSL) were compared with the normal values obtained after 2 or 3 mo of normoxia (N). A static image was created as the sum of the 16-EKG gated images recorded for 10 min in the anterior view of the chest at 20, 60, 120, and 240 min after injection. Regions of interest were located over the heart (H), lungs (L), and mediastinum (M) regions. There was a significant decrease in the H/M and the L/M ratios in RSL compared to N condition. Plasma norepinephrine concentration was elevated during the stay at altitude but not significantly different in RSL compared to N. In conclusion, cardiac [123I]MIBG uptake is reduced after an exposure to altitude hypoxia, supporting the hypothesis of an hypoxia-induced reduction of adrenergic neurotransmitter reserve in the myocardium. Furthermore, the observed significant decrease in pulmonary MIBG uptake suggests an alteration of endothelial cell function after exposure to chronic hypoxia.

Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy.

UNLABELLED: Alterations of cardiac sympathetic innervation are likely to contribute to fatal outcomes in patients with heart failure. These alterations can be evaluated noninvasively by 123I-metaiodoben-zylguanidine (MIBG) imaging. METHODS: The hypothesis that impaired cardiac sympathetic innervation, as assessed using MIBG imaging, is related to adverse outcomes was tested in 112 patients with heart failure resulting from idiopathic cardiomyopathy. Main inclusion criteria were New York Heart Association classes II-IV and radionuclide left ventricular ejection fraction (LVEF) < 40%. Patients were assessed for cardiac MIBG uptake, circulating norepinephrine concentration, LVEF, peak Vo2, x-ray cardiothoracic ratio, M-mode echographic end-diastolic diameter and right-sided heart catheterization parameters. RESULTS: During a mean follow-up of 27 +/- 20 mo, 19 patients had transplants, 25 died of cardiac death (8 sudden deaths), 2 died of noncardiac death and 66 survived without transplantation. The only independent predictors for mortality were low MIBG uptake (P < 0.001) and LVEF (P = 0.02) when using multivariate discriminant analysis. Moreover, MIBG uptake (P < 0.001) and circulating norepinephrine concentration (P = 0.001) were the only independent predictors for life duration when using multivariate life table analysis. CONCLUSION: Impaired cardiac adrenergic innervation as assessed by MIBG imaging is strongly related to mortality. MIBG imaging may help risk stratify patients with heart failure resulting from idiopathic dilated cardiomyopathy.

"Silent" heart failure as observed by a French cardiologist.

As the precursor of overt heart failure, with its grim prognosis, "silent" heart failure is a concept that bears examination. The pathophysiology of congestive heart failure and the mechanisms of the impact of hypertension on the development of left ventricular hypertrophy, and silent and overt heart failure are investigated. In addition, the reasons why diuretics, especially potassium-sparing diuretics such as spironolactone, remain the most effective treatment of mild congestive heart failure, and their role in preventing the evolution of silent to overt heart failure are explained.

Effect of plasma volume expansion on hemodynamics and atrial natriuretic factor release in heart-transplant recipients.

Plasma atrial natriuretic factor (ANF), plasma cyclic guanosine monophosphate (cGMP), plasma aldosterone, plasma-renin activity (PRA) and hemodynamic parameters were measured in heart-transplant recipients and control patients (chest pain syndrome) during right-sided heart catheterization under basal conditions and in response to an intravenous saline load. Basal plasma ANF and cGMP were higher in heart-transplant recipients than in control patients, whereas PRA and plasma aldosterone did not differ. The high plasma ANF levels in heart-transplant recipients did not result from high atrial pressures but appeared to be related with elevated atrial dimensions and cyclosporine-induced renal failure. During volume expansion, plasma ANF increased in control patients and remained elevated during the postinfusion period. In heart-transplant recipients, the changes in plasma ANF were less marked despite identical increases of atrial pressures. The sluggish response of plasma ANF in this group was associated in the postinfusion period with a nonreturn of the hemodynamic parameters to their basal values in contrast with what was observed in control patients.

Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of delayed percutaneous transluminal coronary angioplasty of occluded coronary arteries after acute myocardial infarction.

Whether angioplasty of occluded vessels after myocardial infarction may have beneficial effects on left ventricular function remains unknown. Patients with a first myocardial infarction and thrombolytic therapy who had an occluded infarct-related vessel at delayed coronary angiography were referred systematically for an elective coronary angioplasty performed between 3 and 4 weeks after the myocardial infarction. All patients underwent stress-redistribution-reinjection thallium-201 single-photon emission computed tomography for myocardial viability assessment. Prior angioplasty, a quantitative evaluation of global and regional left ventricular function, was performed. The study group consisted of 38 patients (aged 57 +/- 10 years); 18 had anterior wall infarctions and 20 inferior wall infarctions, but before angioplasty 3 had a patent artery and were excluded. Angioplasty was successful in 30 patients. At follow-up 13 patients (43%) had an occluded coronary artery. In contrast with patients with an occluded coronary artery at follow-up, those with a patent coronary artery had no left ventricular enlargement and had an improvement in both left ventricular ejection fraction (from 48 +/- 9% to 52 +/- 9.8%, p = 0.002) and regional wall motion index (delta = +0.95 SD, p <0.01). In patients with a patent vessel at follow-up, there was a positive correlation between the number of myocardial viable segments and improvement of the infarct zone wall motion (r = 0.52; p = 0.035), and the number of necrotic segments at baseline was positively correlated to the 4-month changes in end-diastolic volume indexes (r = 0.6; p = 0.04). Thus, elective revascularization of occluded coronary arteries with viable myocardium after myocardial infarction improves left ventricular function and lessens remodeling if the artery remains patent during follow-up.

Usefulness of redistribution images in viability detection after acute myocardial infarction.

We undertook this study to evaluate the importance of redistribution images in thallium 201 single-photon emission computed tomography (Tl-201 SPECT) assessment of myocardial viability after acute myocardial infarction. Stress-redistribution-reinjection Tl-201 SPECT was performed in 55 consecutive patients with recent (within 1 month) acute myocardial infarction. The myocardium was divided into 16 segments and activity assessed visually with a score from 0 to 3 on stress-redistribution and stress-reinjection images. A defect was considered moderate if the stress score was 2 and severe if the stress score was 0 or 1. All moderate defects were considered viable, regardless of score on redistribution or reinjection images. Severe defects were considered viable if they were reversible (improvement of 1 score) on redistribution or reinjection images. Stress-redistribution and stress-reinjection images were visually analyzed and compared in terms of viability classification. On visual analysis, 461 segments (52%) were abnormal. One hundred eleven stress defects were moderate; of these, 28 were reversible on reinjection images only and 15 on redistribution images only. However, all of these segments were viable, regardless of the analysis chosen. Of 350 severe stress defects, 48 were reversible on reinjection and irreversible on redistribution images, and 4 were reversible on redistribution and irreversible on reinjection images. Therefore, in viability assessment, 48 segments were misclassified with stress-redistribution analysis, whereas only 4 segments were misclassified using stress-reinjection analysis. Although the usefulness of Tl-201 reinjection imaging is confirmed, redistribution images seem to be of little interest in post-myocardial infarction viability assessment.

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Prehospital use of APSAC: results of a placebo-controlled study.

Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. To give treatment before admission to a coronary care unit, responsibility needs to be transferred from cardiologists to other physicians working in mobile care units. We conducted a 2-part feasibility study to investigate this strategy. Part 1 evaluated the diagnostic accuracy of mobile care unit physicians. Results from this study indicate that with regard to the diagnosis of acute myocardial infarction, the risk of a wrong diagnosis is low. Part 2 was a placebo-controlled trial involving 100 patients in which 57 received anisoylated plasminogen streptokinase activator complex (APSAC) (30 U) at home and 43 received placebo at home. Patients receiving placebo at home were reevaluated on arrival in a coronary care unit and received APSAC (30 U) if indicated. The main results were that (1) diagnostic accuracy was good--all patients had an acute coronary syndrome and 97 of 100 patients had myocardial infarction; (2) time gain was approximately 60 minutes; (3) coronary patency rate was 72%; (4) ejection fraction was higher in the prehospital group (56.7%) than in the control group (53.4%), but the difference was not significant; (5) there was no rhythmic or bleeding complication related to the prehospital treatment; (6) 5 patients died from cardiogenic shock--2 between home and hospital and 3 in the hospital (3 received thrombolytic treatment at home and 2 received placebo at home and APSAC in the hospital); and (7) prehospital administration of APSAC did not induce a delay in arrival to the coronary care unit.(ABSTRACT TRUNCATED AT 250 WORDS)